Anesthesiology is the leading field of medicine in addressing safety, but it still has a long way to go. Despite significant decreases in anesthesia-related mortality, crucial factors remain that pose real hazards to the 21 million Americans that receive general anesthesia each year, and According to the NIGMS, general anesthetics are still among the most dangerous drugs used by doctors, particularly for elderly patients and those with certain chronic, systemic diseases, such as diabetes. It is now clear that the manner in which anesthesia is delivered has a profound impact on safety. Yet, there given a patient population with highly diverse and changing pharmacological differences, practitioners of anesthesia have no direct means of knowing the precise drug plasma levels in the patient at any given time. Thus, there is no direct measure of how to tailor dosing to achieve optimal safety. Such a capability would have a transformative impact, driving the practice of anesthesia to an exacting science that will improve the safety and outcomes of patients. Target controlled infusion systems exist which can automatically adjust doses. However, these are based on a prediction of the plasma drug concentration, by extrapolating from a small model population of healthy patients, leading to major safety concerns, and an absence of FDA clearance. Direct measurement of intravenous concentrations is required to manage these risks and gain market approval. Thus, we propose to develop the first system that directly measures and precisely controls intravenous anesthetic drug concentrations continuously in real-time. We present a disposable system that exploits an aptamer sensor in a microfluidic device that prevents degradation from unmodified whole blood and maintains drift-free quantification with sub-minute time resolution, and nanomolar sensitivity. The completion of Phase I Aims will deliver a proof of concept system, which affirms our ability to measure and control plasma propofol levels in real time in live rabbits, as verified by gold standard LC-MS/MS methods. We will also determine if our feedback-controlled propofol infusion can reduce excursions from a desired depth of sedation versus standard sedation protocol as tested by response to physical stimuli. In Phase II, we will include human subjects to validate our potential to accurately measure propofol levels in humans. We will deliver design improvements and performance metrics, ready for clinical study. We expect to follow on with private capital or strategic investment from a partner company to proceed through clinical stage and FDA clearance via collaboration with industry partners.